A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

Who is this study for? Adult patients with Refractory B Cell Non-Hodgkin's Lymphoma
What treatments are being studied? Anti-CD19 CAR-T Cells
Status: Recruiting
Location: See location...
Intervention Type: Drug, Biological
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Dose expansion Cohorts:

• Cohort B (Burkitt):

• Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma

‣ Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline.

⁃ No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells.

• Participants must have measurable disease as defined below:

‣ Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

• Cohort M/W (Marginal/Waldenström):

• Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)/Waldenström Macroglobulinemia (WM):

• o Participants with indolent lymphomas (nodal or extranodal marginal zone lymphoma, and lymphoplasmacytic lymphoma) must have relapsed after or have been refractory to ≥ 2 prior lines of multi-agent chemoimmunotherapy including prior exposure to an anti-CD20 antibody and an alkylating agent.

• Participants must have measurable disease as defined below:

• o Participants with Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia: must either have PET-positive disease according to Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification or serum monoclonal immunoglobulin M (IgM) paraprotein \> 0.5 g/dL.

• Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia) must have symptomatic disease necessitating systemic treatment.

• In addition, all participants must meet the following criteria:

• CD19-positive by either immunohistochemistry or flow cytometry analysis on any biopsy. If prior anti-CD19 therapy has been administered, CD19-positivity has to be re-established on the most recent biopsy.

• Age ≥18 years at the time of consent.

• Absolute lymphocyte count \> 100/UL.

• Eastern Cooperative Oncology Group (ECOG) performance status \< 2.

• Adequate organ function, defined as:

∙ Adequate bone marrow function for apheresis and lymphodepleting chemotherapy

‣ Hemoglobin \>8 gm/dl (transfusions allowed)

‣ Platelets \>50,000/uL (transfusions allowed)

‣ Absolute Neutrophil Count (ANC) \> 500/uL

‣ alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 3 x institutional upper limit of normal (ULN) and Total bilirubin \< 1.5 mg/dl x institutional ULN, except with Gilbert's syndrome

‣ Serum Creatinine \< 2 x the institutional ULN

‣ Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \> 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) within 3 months of screening. Repeat testing may occur at Investigator's discretion.

• Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line).

• Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-CD19 CAR-T cells.

• Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method.

• Ability to understand a written informed consent document, and the willingness to sign it.

Locations
United States
California
University of California, San Francisco
RECRUITING
San Francisco
Contact Information
Primary
UCSF HDFCCC Cancer Immunotherapy Program
HDFCCC.CIP@ucsf.edu
877-827-3222
Time Frame
Start Date: 2020-09-11
Estimated Completion Date: 2026-10-31
Participants
Target number of participants: 36
Treatments
Experimental: CLOSED TO ENROLLMENT: Dose escalation (CART-T Therapy)
Participants will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated \~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of CAR-T cells at an initial dose of 5 x 10\^5 cells/kg, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years.
Experimental: Dose Expansion: Burkitt, Marginal Zone, or Waldenström Macroglobulinemia ONLY (CAR-T Therapy)
Participants with Burkitt lymphoma, or Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM) will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated \~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of the maximum tolerated dose of CAR-T cells established in the dose escalation phase, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years.
Sponsors
Leads: C. Babis Andreadis
Collaborators: University of California, Davis

This content was sourced from clinicaltrials.gov